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1.
Artigo em Alemão | MEDLINE | ID: mdl-32185450

RESUMO

BACKGROUND: Dementias are among the most feared diseases and pose a threat to social and healthcare systems in aging societies. A cure for Alzheimer's or other dementias will not be achieved in the coming years, which makes prevention of cognitive decline and dementia a priority for research and patient-related services. AIM: Summary of evidence for drug and other compound-related prevention of cognitive decline and dementia. MATERIAL AND METHODS: Literature review of epidemiological evidence and clinical trials of antidementia drugs, anti-amyloid drugs under development, nonsteroidal anti-inflammatory drugs, statins, hormone replacement therapy, lithium, ginkgo biloba, and Fortasyn Connect. RESULTS: There is evidence for effects on single endpoints and subgroups for some of the reviewed compounds, but there is no consistent evidence for efficacy. DISCUSSION: There is no sufficient evidence to provide any specific or general recommendation for drug- or compound-related prevention of cognitive decline or dementia. It needs to be recognized that prevention trials on cognitive decline in aging and dementia require large numbers of participants and long follow-up times, which create major challenges with regard to conducting and financing such trials. The current state of evidence also supports the potential role of nonpharmacological approaches in dementia prevention.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Transtornos Cognitivos/tratamento farmacológico , Demência/tratamento farmacológico , Ginkgo biloba , Nootrópicos/uso terapêutico , Alemanha , Humanos
2.
Life Sci ; 250: 117573, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32209423

RESUMO

Chronic intermittent hypoxia (CIH) is a consequence of obstructive sleep apnea (OSA), which increases reactive oxygen species (ROS) generation, resulting in oxidative damage and neurocognitive impairment. This study was designed to determine whether abnormal iron metabolism occurs in the brain under conditions of CIH and whether Huperzine A (HuA) could improve abnormal iron metabolism and neurological damage. The mouse model of CIH was established by reducing the percentage of inspired O2 (FiO2) from 21% to 9% 20 times/h for 8 h/day, and Huperzine A (HuA, 0.1 mg/kg, i.p.) was administered during CIH exposure for 21 days. HuA significantly improved cognitive impairment and neuronal damage in the hippocampus of CIH mice via increasing the ratio of Bcl-2/Bax and inhibiting caspase-3 cleavage. HuA considerably decreased ROS levels by downregulating the high levels of NADPH oxidase (NOX 2, NOX 4) mediated by CIH. There was an overload of iron, which was characterized by high levels of ferritin (FTL and FTH) and transferrin receptor 1 (TfR1) and low levels of ferroportin 1 (FPN1) in the hippocampus of CIH mice. Decreased levels of TfR1 and FTL proteins observed in HuA treated CIH group, could reduce iron overload in hippocampus. HuA increased PSD 95 protein expression, CREB activation and BDNF protein expression to protect against synaptic plasticity impairment induced by CIH. HuA acts as an effective iron chelator to attenuate apoptosis, oxidative stress and synaptic plasticity mediated by CIH.


Assuntos
Alcaloides/uso terapêutico , Transtornos Cognitivos/tratamento farmacológico , Hipocampo/efeitos dos fármacos , Hipóxia/patologia , Sobrecarga de Ferro/tratamento farmacológico , Sesquiterpenos/uso terapêutico , Animais , Apoptose , Comportamento Animal , Caspase 3/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Modelos Animais de Doenças , Ferritinas/metabolismo , Hipocampo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Plasticidade Neuronal , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo , Oxigênio/metabolismo , Espécies Reativas de Oxigênio , Receptores da Transferrina/metabolismo
3.
Clin Drug Investig ; 40(4): 377-385, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32036587

RESUMO

BACKGROUND AND OBJECTIVE: Cognitive impairments associated with schizophrenia (CIAS) predict poor functional outcomes, but there are currently no approved pharmacological treatments for patients with CIAS. Additional cognitive stimulation may be required for pro-cognitive medications to improve efficacy, and computerized cognitive training (CCT) can be used to increase cognitive activity. A trial evaluating the effects of the novel glycine transporter inhibitor BI 425809 compared with placebo, on a background of regularly self-administered CCT in clinically stable patients with schizophrenia has commenced and its methodology is described here. METHODS: This Phase II, multinational, randomized, double-blind, placebo-controlled, parallel-group trial will randomize 200 clinically stable outpatients, aged 18-50 years with established schizophrenia and no other major psychiatric disorder, 1:1 to BI 425809 or placebo once daily for 12 weeks. Following screening, which included a 2-week CCT run-in period, patients sufficiently compliant with CCT (target: ≥ 2 h of CCT per week during CCT run-in) will be randomized. During the 12-week treatment period, all patients should complete a total of approximately 30 h of CCT. The primary endpoint is change from baseline in neurocognitive function as measured by the neurocognitive composite score of the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB), after 12 weeks of treatment. Secondary endpoints include change from baseline in overall MCCB score, Schizophrenia Cognition Rating Scale, Positive and Negative Syndrome Scale, and safety (adverse events [AEs]) and serious AEs. Primary and secondary endpoints will be analyzed using the Restricted Maximum Likelihood-based mixed model for repeated measures. Novel endpoints include the Balloon Effort Task to evaluate patients' motivation and the Virtual Reality Functional Capacity Assessment Tool to assess skills for daily functioning. DISCUSSION: This is one of the largest and longest trials to date to combine pharmacological therapy with CCT in patients with schizophrenia and will determine the benefit of combining BI 425809 pharmacotherapy with cognitive stimulation through self-administered CCT. This trial will further evaluate whether improvements in neurocognition translate into improved everyday functioning, whether self-administered CCT can be effectively implemented in a large multinational trial, and the role of motivation in neurocognitive and functional improvements. TRIAL REGISTRATION: Registered on Clinicaltrials.gov on March 1, 2019 (NCT03859973).


Assuntos
Cognição/efeitos dos fármacos , Compostos Orgânicos/administração & dosagem , Esquizofrenia/tratamento farmacológico , Adolescente , Adulto , Transtornos Cognitivos/tratamento farmacológico , Método Duplo-Cego , Humanos , Funções Verossimilhança , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
4.
Crit Care Nurs Q ; 43(2): 172-190, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32084061

RESUMO

Traumatic brain injury (TBI) is a leading cause of disability in the United States. With decreasing mortality rates, a higher number of patients are impacted by long-term neuropsychiatric sequelae, such as cognitive deficits, depression, anxiety, and sleep-wake disorders. These sequelae are primarily driven by the disruption of key neurotransmitter homeostasis including dopamine, norepinephrine, serotonin, and acetylcholine. Neurostimulants are centrally acting medications used to assist in restoring these neurotransmitter abnormalities and are pharmacologic options to ameliorate symptoms in post-TBI patients. Examples of neurostimulants include amantadine, selective serotonin reuptake inhibitors, tricyclic antidepressants, central stimulants (ie, methylphenidate), modafinil, and donepezil. Large, well-powered studies have not been performed to validate their use in patients with TBI, leaving uncertainty for these agents' place in therapy. Current practice is driven by consideration of patient-specific factors to select the most appropriate agent. This review provides clinicians with a summary of the available literature on neurostimulants following TBI to guide appropriate usage to help improve patients' symptoms and optimize safety.


Assuntos
Antidepressivos Tricíclicos/uso terapêutico , Lesões Encefálicas Traumáticas/complicações , Transtornos Cognitivos/tratamento farmacológico , Depressão/tratamento farmacológico , Neurotransmissores/uso terapêutico , Inibidores de Captação de Serotonina/uso terapêutico , Ansiedade/tratamento farmacológico , Humanos , Transtornos do Sono-Vigília/tratamento farmacológico
5.
Psychopharmacology (Berl) ; 237(5): 1331-1342, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32034448

RESUMO

RATIONALE: Searches for antidotes to cocaine, and for cognition enhancers potentially applicable to Alzheimer's disease, have revealed a novel regulatory site on nicotinic acetylcholine receptors. In the presence of an agonist, inhibitors binding to this site changed the ion channel equilibrium from the open-channel form towards the closed form. Other, related, molecules could bind to the site without changing the equilibrium. These latter compounds were predicted to displace the inhibitors without affecting receptor function per se. These compounds alleviated the inhibition. One of them is ecgonine methyl ester (EME), which is generally described as inactive, but this work suggested a beneficial effect on cognition. OBJECTIVE: This in vivo study tested for cognitive enhancement by EME in scopolamine-impaired, and aged, rats. METHODS: Memory was the primary endpoint, but thigmotaxis became an important secondary endpoint in the light of observations made during the study. Impaired cognition was pharmacologically induced by scopolamine in young rats, and spontaneously present in aged rats. Learning ability before and after administration of EME was tested in Morris water maze protocols. Concentrations of EME in the brain and plasma were analyzed by gas chromatography-mass spectrometry. RESULTS: A single dose of EME reversed scopolamine impairment, indicating involvement of acetylcholine receptors. Longer-term treatment improved cognition in aged rats, with enhanced rates of learning in the absence of an exogenous cognition-impairing compound. Impairment returned with a new challenge; the improvement could be re-established with continued dosing. EME also reversed thigmotaxis seen in aged rats; thigmotaxis is believed to indicate anxiety. The concentrations of EME in the brain proved adequate drug exposure. CONCLUSIONS: Since other investigators have shown cognition impairment caused by cocaine in aged rats, this work shows that cocaine and EME have opposite effects in Morris water maze models. EME might induce cognitive enhancement and relief of anxiety in cocaine-impaired humans, and in other cognitive disorders.


Assuntos
Envelhecimento/efeitos dos fármacos , Antagonistas Colinérgicos/toxicidade , Cocaína/análogos & derivados , Cognição/efeitos dos fármacos , Entorpecentes/farmacologia , Escopolamina/toxicidade , Envelhecimento/fisiologia , Envelhecimento/psicologia , Animais , Cocaína/farmacologia , Cocaína/uso terapêutico , Cognição/fisiologia , Transtornos Cognitivos/induzido quimicamente , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/psicologia , Inibidores da Captação de Dopamina/farmacologia , Inibidores da Captação de Dopamina/uso terapêutico , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Memória/efeitos dos fármacos , Memória/fisiologia , Entorpecentes/uso terapêutico , Ratos , Ratos Sprague-Dawley
6.
Behav Pharmacol ; 31(1): 81-96, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31923036

RESUMO

Cognitive decline and neurodegenerative diseases pose a significant burden on healthcare resources both in developed and developing countries which is a major socio-economic and healthcare concern. Alzheimer's disease is the most common form of progressive neurodegenerative dementia of the aged brain. Aluminum is a constituent of antacids, deodorants, kitchenware and food additives which allows easy access into the body posing risk to development of senile dementia of Alzheimer's type. Virgin coconut oil was declared as a potential cognitive strengthener. Assessment of cognitive and memory-enhancing effects of virgin coconut oil in senile and young rats to gain vital insights into its effective use in the prevention of neurodegeneration in dementia/Alzheimer's disease-like manifestations and alleviate cognitive dysfunction and learning impairment with neuronal damage imparted by daily oral intake of aluminum. Alzheimer's disease-like symptoms and memory impairment were experimentally induced using oral anhydrous aluminum chloride given daily for five successive weeks in young and old age albino rats. Treatment groups received virgin coconut oil to assess protection during the experimental period. Behavioral test, Morris water maze was conducted before/after induction/treatment. At the end of the experimental period, cholinergic, dopaminergic, noradrenergic and serotonergic neurotransmission as well as brain-derived neurotrophic factor were being investigated, in addition to immunochemical and histopathological examination of targeted brain regions. Virgin coconut oil significantly improved cholinergic activity and monoaminergic neurotransmission. Moreover, immunochemical and histopathological examination revealed marked protection with virgin coconut oil against aluminum-induced Alzheimer's disease-like pathology and cognitive deficit.


Assuntos
Doença de Alzheimer/dietoterapia , Óleo de Coco/farmacologia , Disfunção Cognitiva/dietoterapia , Fatores Etários , Cloreto de Alumínio/efeitos adversos , Doença de Alzheimer/fisiopatologia , Animais , Encéfalo/patologia , Cognição/efeitos dos fármacos , Transtornos Cognitivos/tratamento farmacológico , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/metabolismo , Modelos Animais de Doenças , Alimento Funcional/análise , Masculino , Memória/efeitos dos fármacos , Neurônios/patologia , Ratos , Ratos Endogâmicos
7.
J Diabetes Res ; 2019: 5696391, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31781666

RESUMO

Aim: Type 2 diabetes increases the risk of cognitive decline which adversely impacts self-management of the disease. Evidence also supports a relationship between low serum 25(OH)D levels and poor cognition. The purpose of this trial was to assess vitamin D supplementation on cognitive executive functioning in persons living with type 2 diabetes. Methods: This was a double-blinded RCT where participants were randomized to receive either weekly vitamin D3 supplementation (50,000 IUs) or a matching comparator (5,000 IUs) for three months. The primary outcome was a battery of neuropsychological tests. Serum 25(OH)D was measured by liquid chromatography/tandem mass spectrometry. Repeated assessments of cognitive measures were collected over 12 weeks using alternative testing forms to minimize practice effects. Results: Thirty participants were randomized to either the low-dose allocation (n = 15) or the high-dose allocation (n = 15). Most participants were female (83%) and identified as Black (57%). For all cognition measures, there was no statistically significant finding between participants who received high-dose vitamin D supplementation and those who received low-dose supplementation. However, when assessing cognitive function in both groups over time, minimal improvement on the Symbol-Digits, the Stroop Interference Test, and the Trail Making Test Part B was observed. Conclusions: To our knowledge, this is the first randomized control trial to examine the effects of vitamin D supplementation on cognitive function in people with type 2 diabetes. However, no significant differences in cognitive outcomes between participants who received high-dose therapy and those who received low dose were found.


Assuntos
Colecalciferol/administração & dosagem , Transtornos Cognitivos/tratamento farmacológico , Cognição/efeitos dos fármacos , Diabetes Mellitus Tipo 2/complicações , Deficiência de Vitamina D/tratamento farmacológico , Idoso , Biomarcadores/sangue , Chicago , Colecalciferol/efeitos adversos , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/psicologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/diagnóstico
8.
Handb Clin Neurol ; 165: 253-267, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31727216

RESUMO

The pathophysiology of traumatic brain injury (TBI) can be highly variable, involving functional and/or structural damage to multiple neuroanatomical networks and neurotransmitter systems. This wide-ranging potential for physiologic injury is reflected in the diversity of neurobehavioral and neurocognitive symptoms following TBI. Here, we aim to provide a succinct, clinically relevant, up-to-date review on psychopharmacology for the most common sequelae of TBI in the postacute to chronic period. Specifically, treatment for neurobehavioral symptoms (depression, mania, anxiety, agitation/irritability, psychosis, pseudobulbar affect, and apathy) and neurocognitive symptoms (processing speed, attention, memory, executive dysfunction) will be discussed. Treatment recommendations will reflect general clinical practice patterns and the research literature.


Assuntos
Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/psicologia , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/psicologia , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/psicologia , Antioxidantes/uso terapêutico , Lesões Encefálicas Traumáticas/complicações , Inibidores da Colinesterase/uso terapêutico , Transtornos Cognitivos/etiologia , Humanos , Transtornos Mentais/etiologia , Psicofarmacologia
9.
Int Immunopharmacol ; 77: 105918, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31639616

RESUMO

Alzheimer's disease (AD) is a neurodegenerative disease that affects cognition and behavior. The neuroinflammatory response in the brain is an important pathological characteristic in AD. In this study, we investigated the neuroprotective effects of 1-Methylnicotinamide (MNA), known as the main metabolite of nicotinamide, on reducing lipopolysaccharide (LPS)-induced cognitive deficits via targeting neuroinflammation and neuronal apoptosis. We found that the mice treated with LPS exhibited cognitive deficits in the novel object recognition, Morris water maze and Y-maze avoidance tests. However, intragastric administration of MNA (100 or 200 mg/kg) for 3 weeks significantly attenuated LPS-induced cognitive deficits in mice. Importantly, MNA treatment suppressed the protein expression of nuclear factor-kappa B p65 (NF-κB p65), pro-inflammatory cytokines (TNF-α, IL-6) and decreased the activation of microglia and astrocytes in the hippocampus and frontal cortex of LPS-induced mice. In addition, MNA treatment suppressed neuronal apoptosis by reducing the number of TUNEL-positive cells, caspase-3 activation and increasing the level of Bcl-2/Bax ratio in the hippocampus and frontal cortex. These findings indicate that MNA could be a potential neuroprotective drug in neurodegenerative diseases such as AD.


Assuntos
Anti-Inflamatórios/uso terapêutico , Transtornos Cognitivos/tratamento farmacológico , Transtornos da Memória/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Niacinamida/análogos & derivados , Animais , Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Transtornos Cognitivos/induzido quimicamente , Transtornos Cognitivos/imunologia , Lobo Frontal/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Interleucina-6/imunologia , Lipopolissacarídeos , Masculino , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/imunologia , Camundongos Endogâmicos ICR , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Niacinamida/farmacologia , Niacinamida/uso terapêutico , Fator de Transcrição RelA/imunologia , Fator de Necrose Tumoral alfa/imunologia
10.
Biomed Pharmacother ; 120: 109492, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31593895

RESUMO

Vascular dementia (VD) is a degenerative cerebrovascular disorder, leading to progressive decline of cognitive abilities and memory. Rehmannioside A (ReA) is isolated from Rehmanniae Radix, which exhibits protective role against various diseases. The present study was performed to calculate the possible neuroprotective effects of ReA on VD. Here, the morris water maze (MWM) test and electrophysiological recordings indicated that ReA reduced cognitive deficits. Additionally, through hematoxylin and eosin (H&E) and Nissl staining, ReA attenuated the histological alterations of hippocampus in rats with VD. ReA group significantly reduced oxidative stress, inflammatory response and apoptosis in the hippocampus of rats with VD, which was linked to the activation of nuclear erythroid related factor-2 (Nrf2), while the inactivation of nuclear factor-κB (NF-κB) and Caspase-3. Further, the anti-oxidative, anti-inflammatory and anti-apoptosis abilities of ReA were confirmed in cells stimulated by hydrogen peroxide. Overall, the results above demonstrated the protective effects of ReA against cognitive deficits and indicated the potential value of ReA in the therapy of VD in future.


Assuntos
Apoptose/efeitos dos fármacos , Transtornos Cognitivos/tratamento farmacológico , Disfunção Cognitiva/tratamento farmacológico , Demência Vascular/tratamento farmacológico , Inflamação/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Caspase 3/metabolismo , Cognição/efeitos dos fármacos , Transtornos Cognitivos/metabolismo , Disfunção Cognitiva/metabolismo , Demência Vascular/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Inflamação/metabolismo , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo
11.
Neurol Res ; 41(11): 1024-1033, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31578943

RESUMO

Objective: Diabetes-associated cognitive deficits is characterized by long-term potentiation (LTP) decline in the hippocampus. DL-3-n-butylphthalide (NBP) is a novel agent exerting protective effect against ischemic brain. However, the effects of NBP on diabetes-associated cognitive deficits and underlying mechanisms are not fully clear. This study was designed to evaluate the effects of NBP on the cognitive deficits through activating CaMKII-mediated LTP process and protecting neuron structure of hippocampus in diabetic db/db mice. Methods: Male db/db mice were randomly divided into db/db group (n = 8) and db/db+NBP group (n = 8, 120mg/Kg NBP by gavage). Male db/m mice (n = 8) were included as control group. All animals were treated for 6 weeks. Morris Water Maze test was carried out to evaluate cognitive function. Electrophysiological recordings were performed to test LTP level. HE-staining and electron microscopy of hippocampus were used to observe structure change of neurons and synapse. RT-PCR and Western blot were used to assess the expression of CaMKII, NR2B, and GluR1. Results: Type 2 diabetes mellitus caused LTP decline, and significantly decreased NR2B, CaMKII, and GluR1 expression. Histological analysis showed that disorganized pyramidal cells, as well as degraded neuron and synapse ultrastructure in db/db mice. NBP treatment restored LTP and its associated proteins in db/db mice. The structure changes of hippocampal cells were partly reversed by NBP intervention. Conclusion: These results suggest that NBP ameliorates cognitive deficits induced by type 2 diabetes mellitus through improving CaMKII-mediated LTP and cell ultrastructure in the hippocampus. NBP is a potential therapeutic agent for diabetes-associated cognitive deficits. Abbreviations: NBP: DL-3-n-butylphthalide; LTP: long-term potentiation; CaMKII: calcium/calmodulin-dependent protein kinase II; NR2B: N-methyl-D-aspartic acid receptor subtype 2B; GluR1: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subtype 1.


Assuntos
Benzofuranos/farmacologia , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/efeitos dos fármacos , Transtornos Cognitivos/tratamento farmacológico , Hipocampo/efeitos dos fármacos , Potenciação de Longa Duração/efeitos dos fármacos , Animais , Cognição/efeitos dos fármacos , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Modelos Animais de Doenças , Camundongos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Receptores de N-Metil-D-Aspartato/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/metabolismo , Sinapses/metabolismo
12.
PLoS One ; 14(10): e0223180, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31581202

RESUMO

Cognitive impairments are a common consequence of traumatic brain injury (TBI). The hippocampus is a subcortical structure that plays a key role in the formation of declarative memories and is highly vulnerable to TBI. The α7 nicotinic acetylcholine receptor (nAChR) is highly expressed in the hippocampus and reduced expression and function of this receptor are linked with cognitive impairments in Alzheimer's disease and schizophrenia. Positive allosteric modulation of α7 nAChRs with AVL-3288 enhances receptor currents and improves cognitive functioning in naïve animals and healthy human subjects. Therefore, we hypothesized that targeting the α7 nAChR with the positive allosteric modulator AVL-3288 would enhance cognitive functioning in the chronic recovery period of TBI. To test this hypothesis, adult male Sprague Dawley rats received moderate parasagittal fluid-percussion brain injury or sham surgery. At 3 months after recovery, animals were treated with vehicle or AVL-3288 at 30 min prior to cue and contextual fear conditioning and the water maze task. Treatment of TBI animals with AVL-3288 rescued learning and memory deficits in water maze retention and working memory. AVL-3288 treatment also improved cue and contextual fear memory when tested at 24 hr and 1 month after training, when TBI animals were treated acutely just during fear conditioning at 3 months post-TBI. Hippocampal atrophy but not cortical atrophy was reduced with AVL-3288 treatment in the chronic recovery phase of TBI. AVL-3288 application to acute hippocampal slices from animals at 3 months after TBI rescued basal synaptic transmission deficits and long-term potentiation (LTP) in area CA1. Our results demonstrate that AVL-3288 improves hippocampal synaptic plasticity, and learning and memory performance after TBI in the chronic recovery period. Enhancing cholinergic transmission through positive allosteric modulation of the α7 nAChR may be a novel therapeutic to improve cognition after TBI.


Assuntos
Lesões Encefálicas Traumáticas/complicações , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/etiologia , Receptor Nicotínico de Acetilcolina alfa7/metabolismo , Regulação Alostérica/efeitos dos fármacos , Anilidas/sangue , Anilidas/farmacocinética , Anilidas/farmacologia , Anilidas/uso terapêutico , Animais , Atrofia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Doença Crônica , Transtornos Cognitivos/fisiopatologia , Condicionamento Clássico , Medo , Isoxazóis/sangue , Isoxazóis/farmacocinética , Isoxazóis/farmacologia , Isoxazóis/uso terapêutico , Potenciação de Longa Duração/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto , Memória de Curto Prazo , Ratos Sprague-Dawley , Transmissão Sináptica/efeitos dos fármacos
13.
J Pharmacol Sci ; 140(3): 263-272, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31474557

RESUMO

Atypical antipsychotics improve positive and negative symptoms but are not effective for treating cognitive impairments in patients with schizophrenia. We previously reported that cognitive impairments in neonatal ventral hippocampus (NVH)-lesioned rats show resistance to atypical antipsychotics risperidone and are associated with reduced calcium/calmodulin-dependent protein kinase II (CaMKII) and protein kinase C (PKC) signaling in memory-related regions. The cognitive enhancer ST101 (spiro[imi-dazo[1,2-a]pyridine-3,2-indan]-2(3H)-one) stimulates CaMKII activity in the hippocampus and medial prefrontal cortex (mPFC). We thus tested ST101 on cognitive impairments in NVH-lesioned rats. Chronic ST101 administration (0.1 and/or 0.5 mg/kg, p.o.) significantly improved deficits in prepulse inhibition (PPI), social interaction, and cognitive function in NVH-lesioned rats. ST101 administration (0.5 mg/kg, p.o.) significantly restored the decreased CaMKII autophosphorylation (Thr-286) in the mPFC and hippocampal CA1 regions of NVH-lesioned rats when assessed by immunohistochemistry. Chronic ST101 administration (0.1 mg/kg, p.o.) improved the decline in phosphorylation levels of CaMKII (Thr-286), PKCα (Ser-657), α-amino-3-hydroxy-5-methyl-4-isoxazol- propionic acid (AMPA)-type glutamate receptor subunit 1 (GluA1: Ser-831), and N-methyl-d-aspartate (NMDA) receptor subunit 1 (GluN1: Ser-896) in the mPFC and hippocampal CA1 regions. Taken together, these results suggest that ST101 improves schizophrenia-like behaviors and cognitive impairment by enhancing CaMKII/PKCα signaling in the mPFC and hippocampus in NVH-lesioned rats.


Assuntos
Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Transtornos Cognitivos/tratamento farmacológico , Hipocampo/efeitos dos fármacos , Indanos/farmacologia , Proteína Quinase C-alfa/metabolismo , Esquizofrenia/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Compostos de Espiro/farmacologia , Animais , Animais Recém-Nascidos , Antipsicóticos/farmacologia , Cognição/efeitos dos fármacos , Transtornos Cognitivos/metabolismo , Feminino , Hipocampo/metabolismo , Masculino , Memória/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/metabolismo , Risperidona/farmacologia , Esquizofrenia/metabolismo
14.
Rinsho Shinkeigaku ; 59(9): 570-574, 2019 Sep 25.
Artigo em Japonês | MEDLINE | ID: mdl-31474641

RESUMO

Here, we describe a case involving an 83-year-old woman who was admitted to our hospital for rehabilitation after pseudogout treatment. She had temporal and spatial disorientation. Neuropsychological assessment revealed frontal dysfunction, memory impairment, and executive dysfunction, in addition to general cognitive impairment. Subsequent laboratory examination revealed euthyroid status and elevated titers of anti-thyroid autoantibodies. MRI of the brain revealed no abnormal finding. However, electroencephalography revealed diffuse slowness. We diagnosed Hashimoto's encephalopathy on the basis of the clinical symptoms and laboratory findings. Administration of low-dose prednisolone (5 mg/day) alleviated general cognitive impairment and the laboratory findings; however, memory impairment and construction disorder remained. Previous studies suggest that the characteristics and clinical course of higher brain-function disorder associated with Hashimoto's encephalopathy vary on an individual basis, wherein some patients may respond well to low-dose steroid therapy. Here, we also encountered such a case, that showed good response to a low-dose steroid therapy.


Assuntos
Encéfalo/fisiopatologia , Encefalite/tratamento farmacológico , Encefalite/psicologia , Função Executiva , Glucocorticoides/administração & dosagem , Doença de Hashimoto/tratamento farmacológico , Doença de Hashimoto/psicologia , Prednisolona/administração & dosagem , Administração Oral , Idoso de 80 Anos ou mais , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/etiologia , Eletroencefalografia , Encefalite/complicações , Encefalite/diagnóstico , Feminino , Doença de Hashimoto/complicações , Doença de Hashimoto/diagnóstico , Humanos , Transtornos da Memória/etiologia , Resultado do Tratamento
15.
Rev Infirm ; 68(253): 41-43, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31472785

RESUMO

As part of the 'Legislation, ethics, professional conduct' teaching unit, a group of student nurses analysed the initiative, taken by a nurse, to crush and conceal medicines without the patient's consent, in a context of cognitive disorders. This situation was the focus of a collaborative study involving students and different stakeholders from the training institute.


Assuntos
Transtornos Cognitivos/tratamento farmacológico , Humanos , Consentimento Livre e Esclarecido , Estudantes de Enfermagem
16.
Sci Adv ; 5(9): eaax1912, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31535024

RESUMO

Resident neural stem and progenitor cells, collectively termed neural precursor cells (NPCs), reside in a well-defined neurogenic niche in the subventricular zone (SVZ) and contribute to ongoing postnatal neurogenesis. It is well established that the NPC niche can alter the behavior of NPCs. NPC activation is a promising therapeutic strategy for brain repair. The drug metformin has been shown to activate neural stem cells, promote differentiation, and lead to functional motor recovery in a neonatal stroke model. We demonstrate that metformin-induced NPC expansion and functional recovery is sex hormone dependent. Metformin increases the size of the NPC pool in adult females, but not males, and promotes cognitive recovery in a model of brain injury in females, but not males. Our data demonstrate that metformin has age- and sex-dependent effects on NPCs that correlate with functional recovery, which has important implications for neural repair.


Assuntos
Transtornos Cognitivos/tratamento farmacológico , Metformina/farmacologia , Células-Tronco Neurais/citologia , Neurogênese/efeitos dos fármacos , Neurônios/citologia , Acidente Vascular Cerebral/complicações , Animais , Animais Recém-Nascidos , Diferenciação Celular , Movimento Celular , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/patologia , Modelos Animais de Doenças , Feminino , Hipoglicemiantes/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células-Tronco Neurais/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Transdução de Sinais
18.
Metab Brain Dis ; 34(6): 1747-1759, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31422512

RESUMO

Alzheimer's disease (AD) is the most prevalent neurodegenerative amyloid disorder with progressive deterioration of cognitive and memory skills. Despite many efforts, no decisive therapy yet exists for AD. Safranal is the active constituent of saffron essential oil with antioxidant, anti-inflammatory, and anti-apoptotic properties. In this study, the possible beneficial effect of safranal on cognitive deficits was evaluated in a rat model of AD induced by intrahippocampal amyloid beta (Aß1-40). Safranal was daily given p.o. (0.025, 0.1, and 0.2 ml/kg) post-surgery for 1 week and finally learning and memory were evaluated in addition to assessment of the involvement of oxidative stress, inflammation, and apoptosis. Findings showed that safranal treatment of amyloid ß-microinjected rats dose-dependently improved cognition in Y-maze, novel-object discrimination, passive avoidance, and 8-arm radial arm maze tasks. Besides, safranal attenuated hippocampal level of malondialdehyde (MDA), reactive oxygen species (ROS), protein carbonyl, interleukin 1ß (IL-1ß), interleukin 6 (IL-6), tumor necrosis factor α (TNFα), nuclear factor-kappa B (NF-kB), apoptotic biomarkers including caspase 3 and DNA fragmentation, glial fibrillary acidic protein (GFAP), myeloperoxidase (MPO), and acetylcholinesterase (AChE) activity and improved superoxide dismutase (SOD) activity and mitochondrial membrane potential (MMP) with no significant effect on nitrite, catalase activity, and glutathione (GSH). Furthermore, safranal prevented CA1 neuronal loss due to amyloid ß1-40. In summary, safranal treatment of intrahippocampal amyloid beta1-40-microinjected rats could prevent learning and memory decline via neuronal protection and at a molecular level through amelioration of apoptosis, oxidative stress, inflammation, cholinesterase activity, neutrophil infiltration, and also by preservation of mitochondrial integrity.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Transtornos Cognitivos/tratamento farmacológico , Cicloexenos/uso terapêutico , Hipocampo/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Terpenos/uso terapêutico , Doença de Alzheimer/complicações , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides , Animais , Apoptose/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/metabolismo , Cicloexenos/farmacologia , Fragmentação do DNA/efeitos dos fármacos , Modelos Animais de Doenças , Hipocampo/metabolismo , Inflamação/metabolismo , Masculino , Malondialdeído/metabolismo , Fragmentos de Peptídeos , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Terpenos/farmacologia
19.
Artigo em Russo | MEDLINE | ID: mdl-31464286

RESUMO

AIM: To study the efficacy of recognan (citicoline) in the treatment of cognitive, emotional, autonomic, asthenic disorders in patients with asthenic syndrome. MATERIAL AND METHODS: Thirty-eight subjects (17 men and 41 women), mean age 27.75±12.05 years, with asthenic syndrome (ICD-10 F48.0 - Neurasthenia) were studied. The sample was randomized into 2 subgroups: the main group (n=20) received oral therapy with recognan (100 mg in 1 ml) for 30 days, while the daily dosage was 500 mg (5 ml). In the control group (n=18), no drug therapy was performed. Patient's state was assessed with a large battery of psychological tests and psychometric scales. The follow-up period was 30 days. All participants were examined three times (initially, in the middle of the study (day 15), in the end of the study (day 30)). RESULTS AND CONCLUSION: Asthenic syndrome was detected in 100% of the patients (total asthenia was noted in 70%, decreased activity in 70%, decreased motivation in 40%, physical asthenia in 45%, mental asthenia in 50%). Recognan (citicoline), used for 2 weeks or one month, has a positive effect on the compensation of autonomic, asthenic cognitive and emotional disorders and increases stress resilience of the patients.


Assuntos
Sintomas Afetivos , Transtornos Cognitivos , Citidina Difosfato Colina , Nootrópicos , Adolescente , Adulto , Sintomas Afetivos/tratamento farmacológico , Astenia , Cognição , Transtornos Cognitivos/tratamento farmacológico , Citidina Difosfato Colina/uso terapêutico , Feminino , Humanos , Masculino , Nootrópicos/uso terapêutico , Síndrome , Adulto Jovem
20.
Nutr. hosp ; 36(4): 939-949, jul.-ago. 2019. tab, graf
Artigo em Inglês | IBECS | ID: ibc-184722

RESUMO

In a growing elderly population, mild cognitive impairment (MCI) and age related cognitive decline (ARCD) are increasing in prevalence worldwide. In the search for food compounds able to ameliorate this condition, it has been postulated that n-3 Long chain polyunsaturated fatty acids (n-3 LCPUFA), also known as omega-3, consumption could have a positive effect in the prevention or therapy of these cognitive declines. However, there are contradictory findings in the literature concerning the effects of n-3 LCPUFA on cognitive decline making it difficult to draw a conclusion on this topic. This current systematic review studies the relationship between n-3 LCPUFAs and cognitive status in aged adult and elder populations to determine whether there is or not a positive effect of n-3 LCPUFAs supplementation on cognitive decline. Additionally, we remark how duration periods, different cognitive baseline status in subjects, dosage of n-3 LCPUFAs administration and the presence of other factors might be related to different outcomes. A search of randomized controlled trials (RCTs) related with the relationship between cognitive impairment and n-3 LCPUFA (docosahexaenoic acid, eicosapentanoic acid or combined) supplementation was conducted through PubMed database from January 2010 to December 2017 following the PRISMA statement. Interventional studies which included aged adults or elder subjects with or without MCI and with no previous intake of fish oil supplements (FOS) were included. Ten out of the fourteen RCTs reviewed showed positive outcome on at least one domain of cognitive function (working memory, executive function, verbal memory, short-term memory, perceptual speed, etc.). This systematic review concludes that omega-3 supplementation might have a positive effect on cognitive function. Thus, n-3 LCPUFAs could be used as a preventive or therapeutic tool for cognitive decline in aged or elder adults


En grupos de población de mayores en constante crecimiento, el deterioro cognitivo asociado o no a la edad incrementa en prevalencia mundialmente. Se ha postulado que el consumo de ácidos grasos de cadena larga n-3 (AGCL n-3), también conocidos como omega-3, podrían tener un efecto positivo en la prevención o tratamiento del deterioro cognitivo. Sin embargo, existen hallazgos contradictorios en la literatura respecto al efecto de los AGCL n-3 sobre la función cognitiva, lo cual hace difícil extraer una conclusión sobre su posible función. La presente revisión sistemática estudia la relación entre los AGCL n-3 y el estado cognitivo en adultos de mediana edad y mayores de 60 años para determinar si hay un efecto positivo de la suplementación con omega-3 en el deterioro cognitivo. Adicionalmente, se hace énfasis en cómo la duración de los ensayos, el estado cognitivo basal de los sujetos, la dosis de AGCL n-3 y la presencia de otros factores pudiesen estar relacionados con los diferentes resultados obtenidos. Una búsqueda de ensayos clínicos aleatorizados relacionados con la relación entre el deterioro cognitivo y la suplementación de AGCL n-3 (ácido docosahexaenoico, ácido eicosapentanoico o una combinación de los mismos) se llevó a cabo a través de la base de datos PubMed desde enero de 2010 hasta febrero de 2018 siguiendo la metodología PRISMA. Estudios de intervención que incluían sujetos adultos de mediana edad y mayores de 60 años con o sin deterioro cognitivo leve sin que hubieran recibido otros suplementos (aceite de pescado) fueron incluidos. Diez de los 14 ensayos clínicos aleatorizados mostraron una mejora en algún dominio de la función cognitiva (memoria de trabajo, función ejecutiva, memoria verbal, memoria a corto plazo, rapidez de percepción, etc.). Esta revisión sistemática concluye que la suplementación con AGCL n-3 puede tener un efecto positivo en la función cognitiva. De esta manera, podrían ser usados como una medida preventiva o como tratamiento para el deterioro cognitivo


Assuntos
Humanos , Idoso , Idoso de 80 Anos ou mais , Ácidos Graxos Ômega-3/administração & dosagem , Disfunção Cognitiva/terapia , Envelhecimento Cognitivo , Transtornos Cognitivos/tratamento farmacológico
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